CircBIRC6 facilitates the malignant progression via miR-488/GRIN2D-mediated CAV1-autophagy signal axis in gastric cancer.

Circular RNAs (circRNAs) represent a novel class of non-coding RNAs that play significant roles in tumorigenesis and tumor progression. High-throughput sequencing of gastric cancer (GC) tissues has identified circRNA BIRC6 (circBIRC6) as a potential circRNA derived from the BIRC6 gene, exhibiting significant upregulation in GC tissues. The expression of circBIRC6 is notably elevated in GC patients. Functionally, it acts as a molecular sponge for miR-488, consequently upregulating GRIN2D expression and promoting GC proliferation, migration, and invasion. Moreover, overexpression of circBIRC6 leads to increased GRIN2D expression, which in turn enhances caveolin-1 (CAV1) expression, resulting in autophagy deficiency due to miR-488 sequestration. This cascade of events significantly influences tumorigenesis in vivo. Our findings collectively illustrate that the CircBIRC6-miR-488-GRIN2D axis fosters CAV1 expression in GC cells, thereby reducing autophagy levels. Both circBIRC6 and GRIN2D emerge as potential targets for treatment and independent prognostic factors for GC patients.

Lysosome-Related Genes and RNF19B as Prognostic Markers for Survival and Immunotherapy Efficacy in Hepatocellular Carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) poses a considerable worldwide health concern due to its associated high risk of death. The heterogeneity of HCC poses challenges in developing practical risk stratification tools and identifying prognostic markers for personalized targeted treatments. Recently, lysosomes were shown to be crucial contributors to numerous cellular activities, including tumor initiation and regulating immune responses. Here, we aimed to construct a reliable prognostic signature based on lysosome-related genes and determine its association with the immune microenvironment. METHODS: We comprehensively analyzed lysosome-related genes in HCC to investigate their influence on patient survival and the tumor immune microenvironment. A prognostic signature comprising 14 genes associated with lysosomes was created to estimate the survival outcomes of individuals with HCC. Additionally, we verified the prognostic importance of Ring Finger Protein 19B (RNF19B) in HCC patients through multiplex immunohistochemistry analysis. RESULTS: Our constructed lysosome-related prediction model could significantly discriminate between HCC patients with good and poor survival outcomes (P < 0.05). We also found that elevated RNF19B expression was linked to unfavorable prognostic outcomes and showed a connection with specific clinicopathological characteristics. Moreover, it was observed that RNF19B could facilitate the transformation of macrophages into M2-polarized macrophages and showed a significant positive correlation with PD-1 and CTLA-4. CONCLUSION: In summary, our study proposes that the expression of lysosome-related genes is associated with the immune microenvironment, serving as a predictor for HCC patients' survival. Meanwhile, RNF19B was identified as a novel prognostic marker for predicting OS and immunotherapy effects in HCC patients.

A review of the mechanisms of abnormal ceramide metabolism in type 2 diabetes mellitus, Alzheimer's disease, and their co-morbidities.

The global prevalence of type 2 diabetes mellitus (T2DM) and Alzheimer's disease (AD) is rapidly increasing, revealing a strong association between these two diseases. Currently, there are no curative medication available for the comorbidity of T2DM and AD. Ceramides are structural components of cell membrane lipids and act as signal molecules regulating cell homeostasis. Their synthesis and degradation play crucial roles in maintaining metabolic balance in vivo, serving as important mediators in the development of neurodegenerative and metabolic disorders. Abnormal ceramide metabolism disrupts intracellular signaling, induces oxidative stress, activates inflammatory factors, and impacts glucose and lipid homeostasis in metabolism-related tissues like the liver, skeletal muscle, and adipose tissue, driving the occurrence and progression of T2DM. The connection between changes in ceramide levels in the brain, amyloid ß accumulation, and tau hyper-phosphorylation is evident. Additionally, ceramide regulates cell survival and apoptosis through related signaling pathways, actively participating in the occurrence and progression of AD. Regulatory enzymes, their metabolites, and signaling pathways impact core pathological molecular mechanisms shared by T2DM and AD, such as insulin resistance and inflammatory response. Consequently, regulating ceramide metabolism may become a potential therapeutic target and intervention for the comorbidity of T2DM and AD. The paper comprehensively summarizes and discusses the role of ceramide and its metabolites in the pathogenesis of T2DM and AD, as well as the latest progress in the treatment of T2DM with AD.

Food LEGO: Building hollow cage and sheet superstructures from starch.

The idea of building large structures from small building blocks has had a long history in the human imagination, from the beautifully intricate shells assembled from silica by unicellular algae to the Egyptian pyramids built from stone. Carrying this idea into the food industry has important implications. Here, we introduce a Pickering emulsion platform for building superstructures like hollow cages and sheets using starch granules as building blocks. In food, these superstructures occupy up to six times more space than their constituent parts, thereby delivering a viscosity greater by an order of magnitude than unstructured starch. To achieve this higher viscosity, they use an alternative superstructure mechanism as opposed to the classic swelling mechanism of individual particles. These super-thickeners may reduce calories, cut production costs, and stretch the global food supply, demonstrating how we can design the future by playing with our food.

Combined effects of pre-pregnancy BMI and gestational weight gain on preterm birth: comparison between spontaneous and ART conception.

BACKGROUND: Inappropriate pre-pregnancy body mass index (BMI) and gestational weight gain (GWG) are both linked to preterm birth (PTB); however, which one plays a dominant role in PTB risk is not yet sure. We aimed to evaluate the combined effect of pre-pregnancy BMI and GWG on the risk of PTB in singleton pregnancies conceived both spontaneously and through assisted reproductive technology (ART). METHODS: The data included all mothers (n = 17,540,977) who had a live singleton birth from the US National Vital Statistics System (NVSS) 2015-2019. Logistic regression models, quantile-g-computation, and generalized additive model were used to analyze the combined association of pre-pregnancy BMI and GWG with PTB. RESULTS: The singleton PTB rate was significantly higher in ART pregnancies (11.5%) than in non-ART pregnancies (7.9%). When compared to those women with pre-pregnancy normal weight and GWG within Institute of Medicine (IOM) guidelines, the highest PTB risk was observed in non-ART women with pre-pregnancy underweight and GWG below IOM guidelines (aOR 2.56; 95% CI 2.53-2.60) and in ART women with pre-pregnancy obese and GWG below IOM guidelines (aOR 2.56; 95%CI 2.36-2.78). GWG dominated the combined effect with its joint effect coefficient of - 0.281 (P < 0.05) in non-ART women and - 0.108 (P < 0.05) in ART women. CONCLUSIONS: Inappropriate GWG played a dominant role in increasing the risk of PTB in both non-ART and ART populations. Counseling regarding pre-pregnancy BMI and especially GWG appears to be even more crucial for pregnancies conceived via ART, given their impact on PTB.

The psychiatric symptoms in anti-IgLON5 disease: Case report and literature review.

Immunotherapy may be ineffective in the advanced stages of anti-IgLON5 disease with psychiatric symptoms. The psychiatric symptoms in advanced stages of anti-IgLON5 disease may be associated with neurodegeneration.

Concurrent chronic myelomonocytic leukemia and gastric carcinoma: a case report and literature review.

Background: Chronic myelomonocytic leukemia (CMML) is a rare, malignant, clonal hematopoietic disorder with features of both myelodysplastic syndrome (MDS) and myeloproliferative neoplasm (MPN). It is classified as MDS/MPN overlap syndrome by the World Health Organization (WHO), and the prognosis is generally poor. Solid tumors are rarely associated with or are secondary to CMML. Case Description: We here reported a case of a 75-year-old female patient with persistent peripheral blood monocytosis and bone marrow blasts ≤20%. A diagnosis of CMML was made. Unexpectedly, she presented with recurrent melena and red blood cell (RBC) transfusions were ineffective. Capsule endoscopy revealed gastric space-occupying lesions, and pathological biopsy confirmed gastric adenocarcinoma. Because of the patient's history of coronary heart disease and the fact that she underwent percutaneous coronary intervention with stenting less than half a year ago, the diagnosis and treatment of this patient required a multidisciplinary team of hematologists, oncologists, anesthesiologists and cardiologists. Conclusions: Physicians should consider the possibility of other malignant solid tumors in patients with CMML. For patients at high risk for gastrointestinal endoscopy, capsule endoscopy may be a safer way to determine if a patient needs further endoscopic biopsy. There are currently no guidelines for the treatment of CMML with gastric cancer.

Association of Selenium Levels with Neurodegenerative Disease: A Systemic Review and Meta-Analysis.

BACKGROUND: Neurodegenerative diseases (NDs) have posed significant challenges to public health, and it is crucial to understand their mechanisms in order to develop effective therapeutic strategies. Recent studies have highlighted the potential role of selenium in ND pathogenesis, as it plays a vital role in maintaining cellular homeostasis and preventing oxidative damage. However, a comprehensive analysis of the association between selenium and NDs is still lacking. METHOD: Five public databases, namely PubMed, Web of Science, EMBASE, Cochrane and Clinical Trials, were searched in our research. Random model effects were chosen, and Higgins inconsistency analyses (I2), Cochrane's Q test and Tau2 were calculated to evaluate the heterogeneity. RESULT: The association of selenium in ND patients with Alzheimer's disease (AD), Parkinson's disease (PD), multiple sclerosis (MS), amyotrophic lateral sclerosis (ALS) and Huntington's disease (HD) was studied. A statistically significant relationship was only found for AD patients (SMD = -0.41, 95% CI (-0.64, -0.17), p < 0.001), especially for erythrocytes. However, no significant relationship was observed in the analysis of the other four diseases. CONCLUSION: Generally, this meta-analysis indicated that AD patients are strongly associated with lower selenium concentrations compared with healthy people, which may provide a clinical reference in the future. However, more studies are urgently needed for further study and treatment of neurodegenerative diseases.

Omalizumab for Chinese patients with moderate-to-severe allergic asthma in real-world clinical setting: a prospective, observational study.

BACKGROUND: We aimed to investigate the effectiveness of omalizumab, a monoclonal anti-immunoglobulin E antibody, in Chinese patients with moderate-to-severe allergic asthma in real-world clinical practice. METHODS: This single-centre, prospective, observational study included Chinese patients aged 14-75 years with moderate-to-severe allergic asthma according to the Global Initiative for Asthma criteria. Omalizumab was administered subcutaneously, and the investigator collected real-world data on exacerbations, steroid exposure, pulmonary function and laboratory assessments at weeks 16, 24, 52, 104 and 156 after treatment initiation. The primary outcome was reduced exacerbations, measured as the proportion of patients with exacerbations in the year following omalizumab initiation. Bowker's test for paired proportions was performed to compare exacerbation rates before and after treatment initiation. A generalised linear mixed model was used to compare the number of exacerbations. RESULTS: The mean treatment duration was 46.6 weeks for the full analysis set (n=398). The proportion of patients with exacerbations in the year before and after omalizumab initiation was 80.4% (181/225) and 18.7% (42/225) (difference: -61.8%, 95% CI -68.5 to -54.0, p<0.0001), respectively. At week 52, 67.4% of patients discontinued oral corticosteroids, and 19.5% reduced inhaled corticosteroids. The Asthma Control Test scores increased by 4.6 at week 52 from baseline (p<0.001). Forced expiratory volume in 1 s increased by 11.2% and 9.0% at weeks 24 and 52, respectively, from baseline (p<0.01). Injection site reactions (5.2%) were the most frequently reported adverse event. CONCLUSIONS: In real-world clinical practice, omalizumab treatment remarkably reduced exacerbations in Chinese patients with moderate-to-severe asthma. Omalizumab reduced the use of oral corticosteroids and improved asthma control and pulmonary function.

CircFLNA/miR-214 modulates regulatory T cells by regulating PD-1 in acute lung injury induced by sepsis.

Sepsis-induced acute respiratory distress syndrome (ARDS) remains a major complication of death from bacterial infection. Regulatory T cells (Tregs) are important regulators in addressing lung injury. Considering the extensive research of circular RNAs (circRNAs), the role of circRNA in Treg modulation during ARDS remains unclear. In this study, patients with sepsis-induced ARDS along with non-ARDS controls were obtained, and bronchoalveolar lavage fluid (BALF) was collected as clinical samples. Additionally, cecal ligation and puncture (CLP) was performed to construct a septic ARDS model, and lung tissues as well as peripheral blood were collected. mRNA expressions were measured by RT-qPCR. ELISA was carried out to measure the concentration of inflammatory factors. A combination of online bioinformatics, dual-luciferase reporter, and RND pull-down assays was performed to verify interactions between microRNA (miRNA) and circRNA/mRNA. Tregs were measured by flow cytometry. Our data suggested that circFLNA was aberrantly elevated in ARDS, and depletion of circFLNA upregulated CD4+CD25+Foxp3+ Tregs and decreased inflammatory response. Additionally, miR-214-5p which binds with circFLNA, reversed circFLNA-induced effects in ARDS. Programmed cell death protein 1 (PD-1) is a downstream target gene of miR-214-5p, and abrogated the effects of miR-214-5p on regulating CD4+CD25+Foxp3+ Tregs and inflammatory response. In a word, circFLNA/miR-214-5p/PD-1 signaling is a novel pathway that modulates Tregs in ARDS.

Airway Microbiome Composition and Co-Occurrence Network Are Associated with Inflammatory Phenotypes of Asthma.

INTRODUCTION: The composition and co-occurrence network of the airway microbiome might influence the asthma inflammatory phenotype. Airway microbiota change with asthma phenotypes, and the structure of the bacterial community in the airway might differ between different asthma inflammatory phenotypes and may also influence therapy results. Identifying airway microbiota can help to investigate the role that microbiota play in the asthma inflammatory process. METHODS: Induced sputum from 55 subjects and 12 healthy subjects from Beijing, China, was collected and analyzed for bacterial microbiota. Microbiome diversity, composition, co-occurrence networks, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were predicted and compared between the study groups. RESULTS: Significant differences in the sputum microbiome composition, co-occurrence network, and predicted functional pathways were observed between the two inflammatory phenotypes. Asthmatics in the low FeNO group exhibited lower α-diversity in the sputum microbiota and had higher abundance of the phylum Proteobacteria compared with that of the high FeNO group. The network in the high FeNO group was more "closed" and "connected" compared with that of the low FeNO group, and an alteration in the abundance of keystone species T. socranskii was found. Significantly different predicted metabolic subfunctions including nucleotide metabolism, lipid metabolism, energy metabolism, replication and repair, and drug resistance antimicrobial and carbohydrate metabolism between the two studied phenotypes were also observed. CONCLUSION: Our findings confirm that the airway microbiota is associated with the asthma inflammation process. The differences in the airway microbiome composition and co-occurrence network may affect distinct asthma inflammatory phenotypes, suggesting the possibility that more targeted therapies could be applied based on the airway bacterial genera.

METTL14 reverses liver fibrosis by inhibiting NOVA2 through an m6A-YTHDF2-dependent mechanism.

BACKGROUND: N6-methyladenosine (m6A), the most prevalent internal RNA modification in eukaryotic cells, is dynamically regulated in response to a wide range of physiological and pathological states. Nonetheless, the involvement of METTL14-induced m6A in liver fibrosis (LF) has yet to be established. METHODS: In vitro, HSC cell lines with knock-down and overexpression of METTL14 were constructed, and the effects of METTL14 gene on the phenotypic function of activated HSCs were observed. The proliferation rate was measured by CCK8 and EDU, the cell proliferation cycle was measured by flow detector, the migration rate was measured by Transwell, and the contractility of F-actin was observed after phalloidin staining. The downstream target gene NOVA2 of METTL14 was screened by combined sequencing of MeRIP-seq and RNA-seq, combined with signal analysis. Adeno-associated virus (AAV) was injected into the tail vein in vivo to knock down the expression of METTL14, so as to further observe the role of METTL14 in the progress of LF. RESULTS: our research showed that the methylase METTL14 content was decreased in hepatic tissue from patients with LF, leading to a lowered degree of m6A modification. Functionally, we discovered that knocking down m6A methyltransferase METTL14 led to increased HSC activation and a substantial worsening of LF. Mechanically, as shown in a multiomics study of HSCs, depleting METTL14 levels decreased m6A deposition onNOVA2 mRNA transcripts, which prompted the activation of YTHDF2 to detect and degrade the decrease of NOVA2 mRNA. CONCLUSIONS: METTL14 functioned as a profibrotic gene by suppressing NOVA2 activity in a mechanism dependent on m6A-YTHDF2. Moreover, knocking down METTL14 exacerbated LF, while NOVA2 prevented its development and partly reversed the damage.

Immune checkpoint inhibitors in cancer patients with COVID-19.

Immune checkpoint inhibitors (ICIs) are widely used to treat a variety of cancers and common infectious diseases with high efficacy. During the coronavirus disease 2019 (COVID-19) pandemic, studies suggested that COVID-19 patients may benefit from ICI immunotherapy. However, clinical studies on the safety and efficacy of ICI in COVID-19 patients are still being conducted. Currently, it is not clear whether cancer patients undergoing ICI immunotherapy should adjust their treatment strategy after infection with SARS-CoV-2 and whether ICI can reduce the viral load of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In this study, reports of patients with different types of tumors infected with SARS-CoV-2 under ICI immunotherapy were classified and sorted, including lung cancer, melanoma, squamous cell carcinoma of the head and neck, and hematologic malignances. The safety and efficacy of ICI in antitumor and anti-SARS-CoV-2 therapies were compared and further discussed to provide more reference materials for the application of ICI treatment. In a word, COVID-19 has changed the ICI treatment strategy for cancer patients indeed, and ICI treatment may be a "double-edged sword" for cancer patients complicated with COVID-19.

Understanding animal-based flavor generation, mechanisms and characterization: Cheddar cheese and bacon flavors.

Natural animal-based flavors have great appeal to consumers and have broad applications in the food industry. In this review, we summarized findings related to bacon and Cheddar cheese flavors' components and their precursors, reaction mechanisms, influential factors, and characterization methods. The results show that free sugars, free amino acids, peptides, vitamins, lipids, and nitrites are precursors to bacon flavor. The conditions governing the formation of bacon flavor are thermally dependent, which facilitates the use of thermal food processing to generate such a flavor. For Cheddar cheese flavor, milk ingredients such as lactose, citrate, fat, and casein are reported as precursors. The optimum conditions to generate Cheddar cheese flavor from precursors are quite strict, which limits its application in food processing. As an alternative, it is more practical to generate Cheddar cheese flavor by combining key aroma compounds using thermal food processing. This review provides the food industry the comprehensive information about the generation of bacon and Cheddar cheese flavors using precursor molecules.

Octapeptide repeat alteration mutations of the prion protein gene in clinically diagnosed Alzheimer's disease and frontotemporal dementia.

Studies focusing on octapeptide repeat alteration mutations in PRNP in Alzheimer's disease (AD) and frontotemporal dementia (FTD) cohorts have been rare. We aim to screen sporadic AD and FTD patients with unknown etiology for the octapeptide repeat insertions and deletions in PRNP. Two hundred and six individuals were screened for alterations to the repeat region in the PRNP gene, including 146 sporadic AD and 60 sporadic FTD patients. Our study showed a 1.5% (3/206) occurrence of the octapeptide repeat alteration mutations in PRNP in a Chinese cohort of sporadic dementia. One late-onset FTD patient and one early-onset AD patient each had a two-octapeptide repeat deletion in PRNP, while one early-onset AD patient had a five-octapeptide repeat insertion mutation. PRNP octapeptide repeat alteration mutations are present in sporadic AD and FTD patients. The genetic investigation for PRNP octapeptide repeat alteration mutations in sporadic dementia patients should be carried out in future clinical studies.

Clinical Features of Non-Alcoholic Fatty Liver Disease in the Non-Lean Population.

INTRODUCTION: The prevalence of non-alcoholic fatty liver disease (NAFLD) in non-lean patients is significantly increased, and obesity significantly increases the risk of cirrhosis and HCC in NAFLD patients. However, whether there is a difference in clinical manifestations of NAFLD between overweight and obesity remains unclear. The objective of this study was to assess the clinical and histological features of NAFLD among a non-lean population. METHODS: Current study enrolled consecutive non-lean (body mass index [BMI] >23 kg/m2) patients with NAFLD and available liver biopsy results. Patients were stratified by BMI into two groups for the comparison of their clinical and histological variables, which included the overweight (BMI 23∼<28 kg/m2) and the obese (BMI ≥28 kg/m2). Risk factors for moderate to severe fibrosis (stage >1) were also analyzed through the logistic regression model. RESULTS: Among 184 non-lean patients with metabolic-associated fatty liver disease enrolled, 65 and 119 were overweight and obese, respectively. Patients in the obesity group had a significantly lower level of gamma-glutamyl transpeptidase, higher levels of platelet, glucose, prothrombin time, and more common of moderate to severe inflammatory activity when compared to those in the overweight group. However, a significant low frequency of moderate to severe fibrosis was found in the obesity group versus the overweight group (19.33% vs. 40.00%, p = 0.002). Binary logistics regression analysis of fibrosis found that aspartate transaminase (AST), BMI, alanine transaminase (ALT), and cholesterol (CHOL) were independent predictors for moderate to severe fibrosis in non-lean patients with NAFLD. Compared with the traditional fibrosis-4 (AUC = 0.77) and aminotransferase to platelet ratio index (AUC = 0.79) indexes, the combined index based on AST, BMI, ALT, and CHOL was more accurate in predicting moderate to severe fibrosis in non-lean patients with NAFLD (AUC = 0.87). CONCLUSIONS: Clinical and histological features differed between obesity and overweight patients with NAFLD. When compared to the traditional serum markers, the combination index including AST, BMI, ALT, and CHOL provided a better model to predict moderate to severe fibrosis in non-lean patients with NAFLD.

Comorbidity among inpatients with dementia: a preliminary cross-sectional study in West China.

OBJECTIVE: To investigate comorbidities among hospitalized patients with dementia. METHOD: Data were extracted from the discharge records in our hospital. Comorbidities based on ICD-10 were selected from the Charlson Comorbidity Index (CCI) and Elixhauser Comorbidity Index (ECI). The distributions of these comorbidities were described in dementia inpatients and age- and sex-matched nondementia controls, as well as in inpatients with Alzheimer's disease and vascular dementia. A logistic regression model was applied to identify dementia-specific morbid conditions. RESULTS: A total of 3355 patients with dementia were included, with a majority of 1503 (44.8%) having Alzheimer's disease, 395 (11.8%) with vascular dementia, and 441 (13.1%) with mixed dementia. The mean number of comorbidities was 3.8 in dementia patients (vs. 2.9 in controls). The most prevalent comorbidities in inpatients with dementia compared with those without dementia were cerebral vascular disease (73.0% vs. 35.9%), hypertension (62.8% vs. 56.2%), and peripheral vascular disease (53.7% vs. 31.2%). Comorbidities associated with dementia included epilepsy (OR 4.8, 95% CI 3.5-6.8), cerebral vascular disease (OR 4.1, 95% CI 3.7-4.5), depression (OR 4.0, 95% CI 3.2-5.0), uncomplicated diabetes (OR 1.5, 95% CI 1.4-1.7), peripheral vascular disease (OR 1.8, 95% CI 1.6-2.0), rheumatoid arthritis collagen vascular disease (OR 1.7, 95% CI 1.3-2.3), and anemia (OR 1.2, 95% CI 1.04-1.3). Some comorbidities suggested a protective effect against dementia. They were hypertension (OR 0.8, 95% CI 0.7-0.9), COPD (OR 0.6, 95% CI 0.5-0.6), and solid tumor without metastasis (OR 0.4, 95% CI 0.3-0.4). Vascular dementia has more cardiovascular and cerebrovascular comorbidities than Alzheimer's disease. CONCLUSION: Patients with dementia coexisted with more comorbidities than those without dementia. Comorbidities (esp. cardio-cerebral vascular risks) in patients with vascular dementia were more than those in patients with AD. Specifically, vascular and circulatory diseases, epilepsy, diabetes and depression increased the risk of dementia.

Upper respiratory tract microbiota is associated with small airway function and asthma severity.

BACKGROUND: Characteristics of airway microbiota might influence asthma status or asthma phenotype. Identifying the airway microbiome can help to investigate its role in the development of asthma phenotypes or small airway function. METHODS: Bacterial microbiota profiles were analyzed in induced sputum from 31 asthma patients and 12 healthy individuals from Beijing, China. Associations between small airway function and airway microbiomes were examined. RESULTS: Composition of sputum microbiota significantly changed with small airway function in asthma patients. Two microbiome-driven clusters were identified and characterized by small airway function and taxa that had linear relationship with small airway functions were identified. CONCLUSIONS: Our findings confirm that airway microbiota was associated with small airway function in asthma patients.

Effect of long-term exposure to PM2.5 on the risk of type 2 diabetes and arthritis in type 2 diabetes patients: Evidence from a national cohort in China.

BACKGROUND: It remains unclear whether type 2 diabetes and the complication of arthritis are causally related to the PM2.5 pollutant. Therefore, we aimed to investigate the associations of long-term PM2.5 exposure with type 2 diabetes and with arthritis in type 2 diabetes patients. MATERIALS AND METHODS: This study used data from the China Health and Retirement Longitudinal Survey (CHARLS) implemented during 2011-2018. The associations were analyzed by Cox proportional hazards regression models, and the population-attributable fraction (PAF) was calculated to assess the burden of type 2 diabetes and arthritis-attributable to PM2.5. RESULTS: A total of 21,075 participants were finally included, with 19,121 analyzed for PM2.5 and type 2 diabetes risk and 12,427 analyzed for PM2.5 and arthritis risk, of which 1,382 with newly-diagnosed type 2 diabetes and 1,328 with arthritis during the follow-up. Overall, each 10 µg/m3 increment in PM2.5 concentration was significantly associated with an increase in the risk of type 2 diabetes (HR = 1.26, 95 %CI1.22 to 1.31), and the PAF of type 2 diabetes attributable to PM2.5 was 13.54 %. In type 2 diabetes patients, each 10 µg/m3 increment in PM2.5 exposure was associated with an increase in arthritis (HR = 1.42, 95 %CI: 1.28 to 1.57), and the association was significantly greater than that (H = 1.23, 95 %CI: 1.19 to 1.28) in adults without type 2 diabetes. The PAFs of arthritis-attributable to PM2.5 in participants with and without type 2 diabetes were 18.54 % and 10.69 %, respectively. CONCLUSION: Long-term exposure to PM2.5 may increase the risk of type 2 diabetes and make type 2 diabetes patients susceptible to arthritis.

Anti-contactin-associated protein-like 2 antibody autoimmune encephalitis with rapidly progressive parkinsonism: a case report and literature review.

OBJECTIVE: Anti-contactin-associated protein-like 2 (CASPR2) antibody encephalitis is a rare autoimmune encephalitis (AE) that often presents with epilepsy, cognitive dysfunction, peripheral neuropathy, autonomic nerve damage, and ataxia. Parkinsonism is often observed in neurodegenerative diseases but progresses slowly, and rapidly progressive parkinsonism is rare. Given that it is a curable parkinsonism, identifying and providing early immunotherapy is crucial. METHODS: We reported a patient initially presenting with anxiety and depression, whose symptoms were relieved following mood regulation treatment. After discontinuation of the mood-regulating drugs, mood disorders recurred, accompanied by parkinsonism. The onset of parkinsonism was subacute (< 3-month disease course), and progression was rapid. After immunotherapy, all symptoms disappeared completely. We reviewed all relevant literature on anti-CASPR2 antibody encephalitis with parkinsonism. RESULTS: Our literature review revealed three cases (including our patient): two male and one female, ranging in age from 48 to 72 years. All patients had parkinsonism, generalized tonic-clonic seizures, and hyponatremia. Three patients had anti-CASPR2 antibody positivity in the serum, and one patient had anti-CASPR2 antibody positivity in the CSF. All three patients were treated with anti-epileptic drugs and intravenous steroid pulse therapy, followed by oral steroid therapy, symptoms improved. CONCLUSION: Parkinsonism can be easily misdiagnosed as a neurodegenerative disease, especially during the early stages. In patients with parkinsonism, treatable diseases should be considered in addition to neurodegenerative diseases. In clinical practice, anti-CASPR2 antibody encephalitis should be considered if rapidly progressing parkinsonism is encountered after ruling out common etiologies.